The link between salt-sensitivity/dietary sodium and the development of high blood pressure is widely accepted. However, in spite of the extensive research that has been done in this area, the specific mechanism(s) involved in salt-induced hypertension remain unclear. The long-term goal of this research project is to examine the hypothesis that dietary salt increased blood pressure by modifying vascular reactivity, in part, via enhancement of sympathetic activity and suppression of nitric oxide activity/function. The specific aims are: 1) Examine the mechanism(s) involved in the pathogenesis of salt-induced hypertension with emphasis on cardiovascular, hemodynamics and vascular reactivity, in male and female, conscious and pithed Dahl salt-sensitive and salt-resistant rats. 2) Elucidate the signal transduction pathways and ion channels involved in salt-induced hypertension by nitric oxide, cyclic GMP, neurotransmitter release and Ca/2+ in the isolated aorta. Blood pressure and heart rate will be measured indirectly by tail plethysmography as well as directly in conscious rats. Cardiac output and stroke volume will be measured using a Cardiomax II and total peripheral resistance calculated. Vascular reactivity to sodium nitroprusside, phenylephrine and norepinephrine as influence by -adrenoceptors and sympathetic stimulation as well as the effect of Ca/2+ channel blocker will be evaluated in both conscious and pithed rats. Blood flow to discrete vascular beds (aortic, mesenteric and renal) will be determined using a Transonic flow-meter. Blood samples will be collected from arterial catheters implanted in the femoral arteries. Plasma levels of catecholamine and cGMP will be assayed by high performance liquid chromatography with electrochemical detection and radio-immunoassay, respectively. Cyclic AMP and cGMP levels and intracellular Ca/2+ will also be measure din isolated rat aorta endothelial cells. Data derived from these studies will provide new insights related to gender differences and cardiovascular and cellular mechanism(s) involved in salt-induced hypertension.